The aim of this research program is to investigate mechanisms of protective immunity and immunopathology in schistosomiasis with the ultimate goal of immunologic intervention. Progress was achieved in the following areas during the year. A. Prophylaxis of egg pathology with an IL-12-based vaccine. Immunization of mice with egg antigens plus IL-12 was shown to block egg pathology resulting from subsequent schistosome infection. In a related project, IFN-gamma knockout mice were used to analyze the IFN-gamma dependence of the suppressive effects of IL-12 on egg pathology. B. Identification of calpain as a candidate vaccine antigen. The antigen recognized by a protective T cell clone was identified by screening a recombinant expression library and was shown to be a worm neutral protease, calpain. C. Mechanisms of IL-4 induction in murine schistosomiasis. Using gene knockout mice, the induction of IL-4 by schistosome infection was shown to be independent of B cells and Fc gamma and epsilon receptors on non-B, non-T (NBNT), IL-4-producing cells. In related work a new mechanism of IL-4 induction was identified which involves the triggering of cytokine production from NBNT cells by IL-3 from antigen stimulated CD4+ cells. Finally, the expression of soluble IL-4 receptor was shown to be linked to IL-4 synthesis during murine schistosome infection.